Neuronal effects of stress and modulation of extinction learning in alcohol use disorder (NeuroModel)

酒精使用障碍中压力的神经元影响和消退学习的调节（NeuroModel）

• 批准号: 209303565
• 负责人: Professor Dr. Florian Schlagenhauf
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie (CCM)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/209303565?language=en
• 关键词: Neuronal; effects; stress; modulation; extinction

Alcohol use disorder (AUD) is a chronic condition characterized by compulsive drug use despite adverse consequences and a high relapse risk that remains even after long periods of abstinence. Evidence suggests that stress and exposure to alcohol-associated stimuli contribute to these high relapse rates, however the precise relationship and neuropsychological mechanisms remain insufficiently understood. During the second Funding Period Project 8 (formerly Junior Group) will conduct two studies: 1. During the first Funding Period we demonstrated that patients¿ instrumental choice behaviour is susceptible to the influence of alcohol-associated environmental cues (the so-called Pavlovian-toinstrumental transfer effect, PIT) and confirmed a bias towards habitual behavioural control at the expense of goal-directed behaviour. Both mechanisms are linked to compulsive drug use and relapse in AUD. In healthy controls, stress is reported to bias the balance between goal-directed and habitual behavioural control, and preclinical studies have described effects of stress on PIT. Based on these findings, the aim of the first study of Project 8 is to investigate the influence of acute social stress on habitual control and on PIT in patients with AUD. We hypothesize that stress will further diminish the influence of goal-directed behaviour and related prefrontal learning signals and increase the PIT effect and its associated striatal activation in AUD. Psychosocial stress will be induced using the standardized "Trier Social Stress Test" (TSST) and compared with a control condition using fMRI and a within subject repeated-measures design in AUD patients and matched controls. 2. Pavlovian appetitive conditioning contributes to the motivational power of alcohol-associated cues, therefore potential interventions that target these Pavlovian effects are of great clinical importance. Research on fear extinction is a prime example of successful translational research generating powerful intervention strategies. However, controlled human laboratory studies investigating appetitive conditioning, including effects of drug-associated cues are lacking. The second study of Project 8 will therefore investigate behavioural and neuronal effects of an extinction manipulation on the response to appetitive Pavlovian cues. The effect of a novel memory retrieval-extinction procedure to prevent the reinstatement of extinguished appetitive Pavlovian cues will be compared to a standard extinction procedure and tested in healthy controls.

酒精使用障碍（AUD）是一种以强迫性药物使用为特征的慢性疾病，尽管有不良后果和高复发风险，即使在长期戒酒后仍然存在。有证据表明，压力和暴露于酒精相关的刺激有助于这些高复发率，然而，确切的关系和神经心理学机制仍未充分了解。在第二个资助期内，项目8（原青年组）将进行两项研究：在第一个资助期内，我们证明了患者的工具选择行为容易受到酒精相关环境线索的影响（所谓的巴甫洛夫-工具转移效应，PIT），并证实了以牺牲目标导向行为为代价的习惯性行为控制的偏见。这两种机制都与澳元的强迫性药物使用和复发有关。在健康对照中，据报道，压力会使目标导向和习惯行为控制之间的平衡发生偏差，临床前研究已经描述了压力对PIT的影响。基于这些发现，项目8第一项研究的目的是研究急性社会压力对AUD患者习惯控制和PIT的影响。我们假设压力会进一步削弱目标导向行为和相关前额叶学习信号的影响，并增加AUD的PIT效应及其相关纹状体激活。将使用标准化的“特里尔社会压力测试”（TSST）诱导心理社会压力，并在AUD患者和匹配对照中使用功能磁共振成像和受试者重复测量设计与对照条件进行比较。2. 巴甫洛夫食欲条件反射有助于酒精相关线索的动机力量，因此针对这些巴甫洛夫效应的潜在干预具有重要的临床意义。对恐惧消除的研究是成功转化研究产生强大干预策略的一个主要例子。然而，调查食欲调节的对照人类实验室研究，包括药物相关线索的影响是缺乏的。因此，项目8的第二项研究将调查灭绝操作对食欲巴甫洛夫线索反应的行为和神经元影响。一种新的记忆提取-消失程序的效果，以防止消失的食欲巴甫洛夫线索的恢复将与标准的消失程序进行比较，并在健康对照中进行测试。